Extracellular redox state: refining the definition of oxidative stress in aging
D.P. Jones
Department of Medicine/Pulmonary Division, 615 Michael Street, Suite 205P, Emory University, Atlanta, GA 30322, USA
Oxidative stress in aging can result from an imbalance of prooxidants
and antioxidants with excessive, destructive free radical chemistry.
Thiol systems are important in the control of these processes both by
protecting against the damage and serving in redox signaling mechanisms
to sense the danger and repair the damage. Our studies show that the
redox state of the central antioxidant, glutathione (GSH), can be
quantified under clinical conditions and used as a quantitative index
of oxidative stress. Studies show that plasma GSH/GSSG redox in humans
becomes oxidized with age, in response to chemotherapy and smoking, and
in association with common age-related diseases (type 2 diabetes,
cardiovascular disease). However, the GSH redox is not equilibrated
with the larger plasma cysteine/cystine (Cys/CySS) pool, and the
Cys/CySS redox varies with age in a pattern that is distinct from that
of GSH/GSSG. Furthermore, in vitro studies show that variation in
Cys/CySS redox over the range found in vivo affects signaling pathways
controlling cell proliferation and oxidant-induced apoptosis.
Consequently, the definition of oxidative stress in aging needs to be
refined from the view of a global prooxidant/antioxidant balance to one
that considers balance of specific redox signaling and control
systems. GSH/GSSG and Cys/CySS can be readily measured in humans,
model organisms and cell cultures, and therefore can provide useful
quantitative parameters for operational definition of oxidative stress
to identify key changes in redox signaling and control during aging.
Key words:
Redox signaling, oxidative stress, glutathione, apoptosis, thioredoxin
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